Phosphorus acid ester-containing isonitriles



United States Patent 3,286,000 PHOSPHORUS ACID ESTER-CONTAININGISONITRILES Ivar Ugi and Uwe Fetzer, Leverkusen-Schlebusch, GiinterUnterstenhiifer, Opladen, and Wolfgang Behrenz, Wuppertal-Elberfeld,Germany, assignors to Farbenfabriken Bayer Aktiengesellschaft,Leverkusen, Germany, a German corporation No Drawing. Filed Dec. 16,1963, Ser. No. 330,595 Claims priority, application Germany, Dec. 17,1962,

11 Claims. (Cl. 260-940) The present invention relates to and has as itsobjects new isonitriles having biocidal properties and processes fortheir production.

No compounds have been disclosed so far in the literature Which containphosphorus as well as isonitrile groups in one molecule. In fact, theproduction of those compounds was of no interest, since it is known thatcompounds which contain two biocidal groups in the molecule are lesseffective than analogous compounds containing only one biocidalgrouping.

In accordance with the present invention it has now been found thatphosphorus-containing isonitriles of the formula wherein R denotes aphosphorus-containing organic radical in which the phosphorus iscontained in the form of an ester, thiol ester, thiono ester and/oramide of an acid of 3- or S-Valent phosphorus, possess strong biocidalproperties and can therefore be used as pest control and plantprotecting agents.

Phosphorus-containing isonitriles of the following formulae have provedto be especially effective In the last-mentioned formulae R and R standfor alkyl, alkenyl, aryl, alkoxy, alkylamino or dialkylamino groups or afurther group XA(NC) X stands for oxygen, sulphur, an amino or analkylamino Y stands for oxygen or sulfur,

A stands for an organic radical,

n denotes 0 or 1, and

m stands for a whole number from 1 to 4.

R and R preferably stand for alkyl radicals with l to 6 carbon atoms,the phenyl radical, alkoxy radicals with 1 to 6 carbon atoms as well asfor alkylamino radicals with 1 to 6 carbon atoms and dialkylaminoradicals with 2 to 12 carbon atoms.

A preferably stands for aromatic radicals, such as the phenyl radical,aliphatic radicals, especially with 1 to 10 carbon atoms, andaraliphatic radicals with 7 to 12 carbon atoms. These radicals may befurther substituted, for example by alkoxy, aroxy, alkylamino andcarbalkoxy groups as well as by halogen atoms, nitrile and nitro groups.

It has further been found that the organic isonitriles according to theinvention are obtained by treating phosphorus-containing formamides ofthe formula (IV) R (NHCHO) wherein R and m have the meaning indicatedabove, in the presence of bases with agents splitting off water.

Those phosphorus-containing formylamides are preferably used which canbe converted into the phosphoruscontaining isonitriles according toFormulate II and III.

It is definitely surprising that the phosphorus-containing isonitrilesaccording to the invention exhibit such a high biocidal activity.Furthermore it is especially surprising that they are much more effectvethan analogous compounds which contain only the phosphorus grouping oronly the isonitrile grouping. In contrast to the teaching according tothe state of the art, a mutual reinforcement of the biocidal groupingstakes place in the compounds according to the invention.

When the process according to the invention is carried out with0,0-diethyl-O-(4-formylamidophenyl)-thiono phosphate and with phosgeneas an agent splitting off water the course of the reaction can beillustrated by the following scheme of formulae:

CZH O IS The starting substances for the process according to theacylation. This reaction is expediently carried out in the presence ofbases and of a solvent, such as. chlorinated.

hydrocarbons or tert. butanol, at temperatures in .the

range of 0 to 50 C. A few representative examples fork the preparationof phosphorus-containing formylarnides are given in the examples.

The following phosphorus-containing isonitriles can be produced, forexample, by the method according to the invention:

0,0-diethyland -dimethyl--(2-isocyanoethyl)-phosphate and thecorresponding thiono-, thioland thionothiolphosphates, 0,0diethyl-O-(2-methyl-2-isocyano-lpr-opyl)phosphate and the correspondingthiono-, thioland thionothiolphosphates; the cyclic ester from 0-methyl-phosphoric acid and 2 methyl-2-isocyano-1,3- propanediol;0,0-diethyl 0 (4-isocyanophenyl)-phos phate and -thion-o-phosphate,0,0-diethyl-0-(Z-methyl-S- isocyanophenyl)phosphate and-thionophosphate; 0,0- diethyl-O-(4-isocyano-anilide)-thionophosphoricacid ester; 0,0-diethyl 0 (3,5-dimethyl-4-isocyanophenyl)-thionophosphate; 0,0 (2,2 diisocyano-)diethylphosphite, 0,0(2,2'-diisocyano-)diethyl-0-(2",2"-dichlorovinyl-) phosphate,0,0,0-(2,2-diisocyano-)triethyl-phosphate;0,0,0-(2,2,2"-triisocyano)-triethylphosphate and -thionophosphate;0,0,0-(4,4',4"-triisocyano-)triphenylphosphate and -thionophosphate,0,0dimethyl-S-(4isocyano 2 thia-l-butyl)-thionothiolphosphate,0,0-dimethyl S (3-methyl-4-isocyano-5-ethylphenyl)-thiolphosphate,dithiol 0 (2-isocyano-ethyl)-thiono-S,S- (quinoxaline 2,3 phosphate, 0(2 isocyanoethyl)- thiono S,S (1,4 napthoquinone 2,3-) dithiolphosphate,0,0 di-(2-isocyanoethyl)-S-(N-methylaminocar-'bonyl-rnethyL)thionothiolphosph'ate, phosphoric acid-0-(2-isocyano-isobutyl-ester) N,N,N',N' tetramethyl-diamide. S (dimethylthionophosphoryl)-1-mercaptosuccinic acid-di-0,0-(2isocyanoethyl)-ester, 0,0-diethyl(2,4-diisocyano-3,S-dimethyhphenyl)-thionothiolphosphate, S(dimethyl-thiono-phosphoryl)-thioglycollic acid 2 isocyano-isobutylester, 0,0-dimethyl-0-(5-isocyano-3-thia-1-pentyl)-thionophosphate,0,0-dimethyl-S- (5 isocyano-3-thia-pentane-1-)thiol-phosphate, 0,0-di-(2 isocyanoethyl) S (Z-phenyI-Z-thiaethane-l-)-thionothiolphosphate, 1-isocyano-isobutyl-phosphonic acid- 0,() diethyl ester,0,0,0-tri-(2-isocyanoisobutyl)-thionophosphate.

The process according to the invention is expediently carried out in thepresence of inert solvents. Suitable for this purpose are: hydrocarbons,such as petroleum ether and benzene; chlorinated hydrocarbons, such asethylene chloride and chloroform; and ethers such as diethyl ether anddioxane. Suitable agents for splitting off water are acyl halides suchas phosgene, phosphoryl chloride, benzene-sulphonyl chloride andcyanuric chloride. As bases there may be used, for example, pyridine,triethylamine and potassium-tert. butylate. The most advantageous agentfor splitting oil water is phosgene in combination with trialkylamines,such as trimethylamine and triethylamine.

The reaction according to the invention can be carried out within afairly wide range of temperature; it is generally performed attemperatures between 40 C. and 100 0, preferably between and 30 C.

For the preparation of the phosphorus-containing isonitriles, 0.9 to 1.1mols of phosgene and 1.8 to 3.0 mols of base are used for every mol offormylamide, working in the presence of 300 to 1000 cc. of solvent.However, deviations from these molecular proportions are possible.

Instead of the phosphorus-containing formylamides there may also be usedacylating derivatives of acids of 3- and 5-valent phosphorus incombination with formylamides carrying acylatable hydroxyl, thiol oramino groups. In this case the starting products proper are prepared inthe reaction vessel immediately before the reaction according to theinvention.

The organic isonitriles according to the invention have strong biocidalproperties. They can therefore be used as pest control and plantprotecting agents. They are especially effective against animal pests,such as insects, worms and mites. For example they can be used for thedestruction of flies, aphids, spider mites, caterpillars, mosquito,crickets, ticks, grain weevils and mosquito larvae. The inventivecompounds are distinguished by a strong contact-insecticidal activityand also by a systemic action. On account of their fungicidal propertiesthey are also suited for combating fungi. Most surprisingly they are ofremarkable low toxicity against warm-blooded animals.

The compounds according to the invention can be applied as such orformulated in usual manner. They may be used in the same manner as otherknown phosphoric insecticides, i.e. in a concentration from about0.00001% to about 1%, diluted or extended with suitable solid or liquidcarriers or diluents in the form of suspensions, dispersions, powdersand dusts. Examples of solid carriers are talc, chalk, bentonite, clayand the like, as liquid carriers there may be mentioned water (ifnecessary with commercial emulsifiers), alcohols, especially loweralcohols such as methanol or ethanol, ketones especially lower ketonessuch as acetone or methyl ethyl ketone, liquid hydrocarbons and thelike. The new compounds may furthermore be used in combination with eachother or with known insecticides, fertilizers etc.

In the following Table 1 the efiect of 0,0-diethyl-0- (2isocyano-Z-methyl-l-propyl)-thionophosphate against various pests isgiven as an example for the special utility.

Aqueous dilutions of this compound have been prepared by mixing theactive ingredient with the same amount of dimethyl formamide as anauxiliary solvent adding thereto 20% by weight referred to active ingredient of a commercial emulsifier consisting of a benzyl hydroxypolyglycol ether containing about 10 to 15 glycol ethers, and dilutingthis premixture at last with water to the desired concentrationindicated in the following paragraphs:

The tests have been carried out as follows:

(a) Against flies: about flies (Musca domestica) are placed undercovered petri dishes in which drip Wet filter papers have been placedwhich are sprayed with insecticidal solutions of concentrations as shownbelow.

(b) Against mosquitoes of the type Aedes aegypti: about 8 to 12mosquitoes are placed under covered petri dishes in which drip wetfilter papers have been placed which have been sprayed with aninsecticidal solution prepared as indicated above and in a concentrationas shown below.

(c) Against American cockroaches: about 3 cockroaches are placed undercovered petri dishes in which drip wet filter paper has been placedwhich is sprayed with an insecticidal solution prepared as indicatedabove and in a concentration as shown below. The living status of thecockroaches has been determined after 24 hours.

1) Against grain weevils: about 20 pests were placed under covered petridishes in which drip wet filter paper has been placed. The filter paperis sprayed drip wet with an insecticidal solution as indicated above andin a concentration as shown below. The living status of the grainweevils has been determined after 24 hours.

(e) Against larvae of flies (Musca dOmeslica): about 10 -fly larvae areplaced under covered petri dishes in which drip wet filter papers havebeen placed which were sprayed with an insecticidal solution of aconcentration as shown below and prepared as indicated above. Evaluationoccurred after 10 days.

(f) Again-st mosquito larvae of the type Aedes aegypti: about 20 larvaewere brought into diluted aqueous emulsions prepared as described above.Counting of the dead pests occurred after 24 hours.

(g) Against aphids (contact insecticidal action) of the type Doralisfabae: heavily infested bean plants (Vicia faba) have been sprayed dripWet with solutions as prepared above. The effect has been determined byevaluation after 24 hours by counting the dead pests either on thesurface of the soil or still remaining on the plants.

The tests of the other pests have been carried out in usual manner.

TABLE I Cone. of Insecticidal active Lethal efiect No. Kind of pestsingredient time 1 (destruction in percent TL of pests in percent) (1)House fiies (Musca domestica) 0.1

0. 001 (2). Mosquitoes (Aedes aegypii) 8.6

(3).--" American cockroaches (Perz'planeta emeri- 0. 1

cans

(4) Crickets (Gryllus domesticus) 0.1 100 0. 01 100 (5). Grain weevils(Caltmdra granaria) O. 1 100 (0). Larvae of flies (Musca domestica) 0. 1100 (7) Mosquito larvae (Aedes aegypti) 0. 01 100 0.001 50 (8) Aphids(Doralis fabae) 0.2 90 (9) Fruit flies (Drosophila melanogaster) 0.2 1000. 02 100 (10)..-. Aphids on oats (Sitobium granarium) 0.2 100 1 Lethaltime, L'Iwn is the time in which 100% of the pests are killed.

The following Table II gives as a further representative example theeffect of 0,0-diethyl-O-(3-is0cyano-1- propyl)-phosphate, and thesubsequent Table III gives as a representative example the eifect of0,0-diethyl-O- (2 isocyano ethyl)-thiono-phosphate against variouspests.

highly reduced pressure. The yield amounts to 82 g. of a pale yellow oilof HP. 70 to 75 C./0.004 mm. Hg,

consisting mainly of0,0-diethyl-O-(Z-methyl-Z-isocyanol-propyl)-thionophosphate besides alittle 0,0-diethyl- O-(Z-methyl-Z-isocyano-1-propane)thiolphosphate.

The 2-methyl-2-N-forrnyl-amido-l-propanol to be used TAB LE 11 Cone. ofInsecticidal active Lethal effect N Kind of pests ingredient time 1(destruction in percent TL of pests in percent) (1) House flies (Muscadomestica) $1 (2) Crickets (Gryllus domesticus) 0: 1 (3) Mosquitoes(Aedes aegypti) s $1 0: 001 (4) Mosquito larvae (Aedes aegypti) 0.001

TABLE III Cone. of Insecticidal active Lethal elicct N Kind of pestsingredient time 1 (destruction in percent 'IL n of pests in percent) (1)House flies (Musca domestica) 0. 1 (2) Crickets (Gryllus domesticus) 0.1 (3) Mosquitoes (Andes acgypti) g. 31

0: 001 (4) Mosquito larvae (Aedcs aegypt'i) 0. 001

1 Lethal time, L'Tmo is the time in which 100% 01 the posts are killed.

The following examples are given for the purpose of illustrating theinvention.

Example I 0 11 0 s CH PO-CHzC-CH;

0211 0 NC A solution of 117 parts by weight of Z-me-thyl-Z-N-formylamido-l-propanol in 390 parts by weight of triethylamine and 1000parts by weight of methylene chloride is treated, while cooling with iceand stirring, with 188.5 parts by weight of 0,0-diethyl-thionoph0sphoricacid ester chloride. The reaction is completed by boiling the mixtureunder reflux for minutes. 100 parts by weight of phosgene aresubsequently introduced into the mixture while stirring and cooling itwith ice. After the addition of ice-water, the methylene chloride layeris separated, dried over magnesium sulphate, concentfated in a vacuum,and the residue is distilled under as starting material is prepared, forexample, by reacting Z-aminoisobutanol with the stoichiometric amount offormic acid in boiling toluene while distilling oil the reaction water.After distilling olf the solvent in a vacuum, the compound is obtainedwhich possesses a melting point of 45 to 47 C.

Example 2 0H, CaHsO 0 gene are then introduced at to 15 C. withstirring. After the addition of water, the organic phase is separated,dried over anhydrous magnesium sulphate and concentrated in a vacuum,137 g. of a brown oil re main. From a g.-sample of this product a smallamount of pure 0,0-diethy1-O-(2-methyl-5-isocyanophenyl)-phosphate of BR142 to 145 C./0.02 mm. Hg can be separated by distillation (with partialdecomposition) in a high vacuum.

The 3-hydroxy-4-methyl-formanilide used as starting material isprepared, for example, by heating 190 parts by weight ofpotassium-Z-methyl-S-formylamidophenolate with 188.5 parts by weight of0,0-diethyl chloro-thionophosphate in 700 parts by weight of tert.butanol for 1 hour under reflux. The reaction solution is shaken withwater, the organic phase separated, dried and subjected to a vacuumdistillation. The resultant 3- hydroxy-4-methyl formanilide cansubsequently be used immediately for the reaction according to theinvention.

Example 3 172.5 parts by weight of 0,0-diethyl phosphoric acid esterchloride are added dropwise at 5 to C., while stirring and cooling themixture with ice, to a solution of 89 parts by weight ofZ-N-formylamido-ethanol and 330 parts by weight of triethylamine in 700parts by weight of methylene chloride. The mixture is subsequentlyheated at boiling temperature for 1 hour, cooled in an ice-bath to 5 C.,and a solution of 99 parts by weight of phosgene in 200 parts by weightof methylene chloride is allowed to run in slowly. Subsequently themixture is heated at 40 C. for 1 hour While passing through nitrogen.The mixture is then filtered off with suction, the filtrate treated with500 parts by weight of petroleum ether, again filtered off with suction,concentrated in a vacuum at a bath temperature of 60 C., and distilledunder highly reduced pressure. A water-clear liquid of BR 70 to 71 C./0.01 mm. Hg is obtained. The yield amounts to 62.5 parts by weight of0,0-diethyl-O-(2-isocyano-ethyl)- phosphate.

The 2-N-formylamido-ethanol used as starting material is prepared, forexample, from Z-amino-ethanol and formic acid methyl ester by boilingthese compounds under reflux for 4 hours. The reaction mixture isdistilled in a vacuum. The 2-Nformylamido-ethanol obtained has a boilingpoint of 155 C./0.3 mm. Hg.

Example 4 1 -0 C zII-1-N 0 188.5 parts by weight of0,0-diethyl-thionophosphoric acid ester chloride are added dropwise at40 to 45 C. with stirring to a mixture of 750 parts by weight ofmethylene chloride, 330 parts by weight of triethylamine and 89 parts byweight of 2-N-formylamido-ethanol (see Example 3), and the mixture isboiled under reflux for 3 hours. 32 parts by weight of phosgene in 100parts by weight of methylene chloride are then added drop- Wise at 5 to10 C. to the mixture with stirring. The mixture is then heated at 40 C.for 1 hour while passing through nitrogen, and treated with 200 parts byweight of ice-water. After separation of the layers, the organic phaseis again washed with water, dried over sodium sulphate and concentratedin a vacuum at a bath temperature of 60 C. As the residue there remain37 parts by weight of a brown oil consisting to about 95% of0,0-diethyl-O-(2-isocyanoethyl)-thionophosphate.

Example 5 CZI'ISO sl 55 parts by weight of phosgene in 150 parts byweight of methylene chloride are allowed to run at 5 to 10 C. whilestirring into a mixture of 139 parts by weight of 0,0 diethyl O (4 Nformylamidophenyl)- thionophosphate, 115 parts by weight oftriethylamine and 750 parts by weight of methylene chloride. The mixtureis heated at 40 C. for 1 hour while passing through nitrogen, and thenhydrolysed with 500 parts by Weight of ice-water. The layers areseparated, the organic phase is washed three times with water, driedover sodium sulphate and concentrated in a vacuum at a maximumtemperature of 60 C. 123 parts by weight of a deep brown liquid areobtained which is not distillable and consists to about of0,0-diethyl-O-(4- isocyano-phenyl)-thionophosphate. The 0,0-diethyl-O-(4-N-formylamidophenyl)-thionophosphate used as starting material isprepared by reacting 137 parts by weight of 4-N-formylamidophenol with188.5 parts by weight of 0,0-diethyl-thionophosphoric acid esterchloride in the presence of a potassium-tert. butylate solution (from 39parts by weight of potassium and 900 parts by weight of tert. butanol),at about 80 C. for 2 hours. In order to work up the reaction mixture itis first filtered and then distilled off in a vacuum with butanol. Theresidue obtained can be used immediately for the reaction according tothe invention.

Example 6 39 parts by weight of potassium are dissolved in 800 parts byweight of tert. butanol. First 151 parts by weight of3-N-formylamido-4-methyl-phenol and then 160.5 parts by weight of0,0-dimethyl-thionophosphoric acid ester chloride are introduced intothis solution at about 0 C. with stirring. After boiling the mixtureunder reflux for 1 hour, it is cooled to 0 C., treated with 125 parts byweight of triethyl-amine, and then parts by weight of phosgene areintroduced. When the reaction is completed, 200 parts by weight ofhenzene and 400 parts by weight of a 20 to 30% soda solution are added,the product is separated, dried over anhydrous magnesium sulphate,filtered and concentrated in a vacuum at 20 to 30 C. The yield amountsto 245 parts by weight of crude 0,0-dimethyl-O-(3-isocyano-4-methyl-phenyl)-thionophosphate.

Example 7 20 parts by weight of phosgene are introduced at 5 to 10 C.with stirring into 45.8 g. of crude 0,0-dimethyl S (2 N formylamidoethyl) thionothiolphosphate, 350 parts by weight of methylene chlorideand 45 parts by weight of triethylamine. After 1 hour the mixture isheated to boiling while blowing through nitrogen, and then treated With500 parts by weight of icewater. The layers are separated, the organicphase is washed with water, dried over magnesium sulphate and thesolvent evaporated in a vacuum. As a residue remain 41 parts by weightof crude 0,0-dimethyl-S-(2- isocyano-ethyl)-thionothiolphosphate of BF.75 C./ 0.02 mm. Hg (with partial decomposition). Preparation of thestarting material:

79 parts by weight of 0,0-dimethyl-thionothiolphosphoric acid aredissolved in parts by weight of formic acid methyl ester and 21.5 partsby weight of ethylene imine are added dropwise at C. while stirring. Themixture is allowed to reach room temperature and is finally heated atboiling temperature for 3 hours. After evaporation of the solvent in avacuum, 110 parts by weight of a colourless oil remain, which consistsof 0,0 dimethyl S (2 N formylamido-ethyl)- thionothiolphosphate.

What is claimed is:

1. A compound of the formula wherein R and R stand independently for amember selected from the group consisting of alkoxy having up to 6carbon atoms, alkyl having up to 6 carbon atoms and the group Y standsfor oxygen or sulfur, n stands for zero or one, In stands for an integerfrom 1 to 4, X stands for oxygen or sulfur and A stands for a memberselected from the group consisting of lower alkyl having up to 6 carbonatoms, phenyl and lower alkyl substituted phenyl.

2. A compound according to claim 1 wherein R and R stand for alkoxyhaving up to 6 carbon atoms or isocyano-substituted alkoxy having up to6 carbon atoms.

3. A compound according to claim 1 wherein R and R stand for alkoxyhaving up to 6 carbon atoms or isocyano-substituted alkoxy having up to6 carbon atoms, n stands for one, m stands for one and A stands foralkyl having up to 6 carbon atoms.

4. A compound according to claim 1 wherein R and R stand for alkoXyhaving up to 6 carbon atoms or isocyano-substituted lower alkoxy havingup to 6 carbon atoms, n stands for one, In stands for one, X stands foroxygen and A stands for phenyl or alkyl substituted phenyl having up to4 carbon atoms in the alkyl group.

5. A compound of the formula 6. A compound of the formula on, 021150 s to oaHso 7. A compound of the formula O C zHr-NC 021150 8. A compound ofthe formula CzH O s i o CzHr-NC 9. A compound of the formula onzr o s 0No olrno 10. A compound of the formula wmmng-o-Qon,

11. A compound of the formula oH,o s

on o SCHQCHZNC References Cited by the Examiner CHARLES B. PARKER,Primary Examiner. JOSEPH P. BRUST, Examiner.

RICHARD L. RAYMOND, Assistant Examiner.

1. A COMPOUND OF THE FORMULA